Anti-inflammatory effects of U74389F in a rat model of intestinal ischemia/reperfusion injury.

Abstract

OBJECTIVE:

To investigate the role of eicosanoid generation and neutrophilic infiltration in the protective effects of U74389F against ischemia/reperfusion injury in the small intestines of rats.

DESIGN:

Prospective, randomized, controlled study.

SETTING:

University research laboratory.

SUBJECTS:

Adult, male Sprague-Dawley rats weighing between 200 and 300 g.

INTERVENTIONS:

Groups (5-8) of rats treated with U74389F or vehicle were subjected to a sham operation and 30 mins of ischemia by occlusion of the superior mesenteric artery or 30 mins of ischemia followed by 60 or 120 mins of reperfusion. U74389F (2.5 mg/kg i.v.) or vehicle (citrate buffer) were slowly injected 2 mins before ischemia.

MEASUREMENTS AND MAIN RESULTS:

Ischemia significantly (p < .05) increased mucosal injury (0 [normal] to 5) in both U74389F and untreated rats. In contrast, U74389F significantly (p < .05) attenuated the severity of injury after reperfusion. In vehicle-treated rats, ischemia/reperfusion significantly reduced villus height in both U74389F and untreated groups. However, the surface epithelial layer was intact in the U74389F but not in the vehicle-treated group. In addition, compared with the vehicle-treated group, U74389F significantly reduced neutrophil infiltration and prevented the increase in leukotriene B4 and prostaglandin E2 in response to ischemia and reperfusion.

CONCLUSIONS:

This study demonstrates that the mechanism of U74389F against mesenteric ischemia/reperfusion includes a delay and reduction of neutrophilic infiltrate, an inhibition of leukotriene B4 production, and a facilitation of mucosal restitution.

• Authors: A Stojadinovic, R Smallridge, J Nath, X Ding, T Shea-Donohue
• Journal: Critical care medicine (Crit Care Med) Vol. 27 Issue 4 Pg. 764-70 (Apr 1999) ISSN: 0090-3493 [Print] United States
• PMID: 10321667 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Eicosanoids
• Immunosuppressive Agents
• Pregnatrienes
• U 74389F
• Leukotriene B4
• Dinoprostone

Topics

• Animals
• Antioxidants (therapeutic use)
• Dinoprostone (blood)
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Eicosanoids (biosynthesis, immunology)
• Immunosuppressive Agents (therapeutic use)
• Inflammation (immunology)
• Injections, Intravenous
• Intestine, Small (blood supply)
• Leukotriene B4 (blood)
• Male
• Neutrophil Activation (drug effects, immunology)
• Pregnatrienes (therapeutic use)
• Prospective Studies
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (blood, immunology, pathology, prevention & control)